Hypermethylation of the GSTP1 promoter region in breast cancer is associated with prognostic clinicopathological parameters

Lasabová, Zora; Tilandyova, Petra; Kajo, Karol; Žúbor, Pavol; Burjanivová, Tatiana; Danko, Ján; Plank, L

doi:10.4149/neo_2010_01_035

Cited by 22 publications

(14 citation statements)

References 30 publications

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“…GSTP1 belongs to a family of metabolic enzymes and is involved in the detoxification of carcinogens and chemotherapeutic agents by conjugating them with glutathione [33]. In female breast cancer, GSTP1 hypermethylation is correlated with high-grade ductal carcinoma in situ and high-grade invasive breast cancer, presence of lymph node metastasis and poor outcome [4,30,34,35]. ER, encoded by ESR1 , is an important factor in breast cancer, because studies in females have shown that patients with hormone-negative tumors do not benefit from endocrine therapy [36].…”

Section: Discussionmentioning

confidence: 99%

Promoter hypermethylation in male breast cancer: analysis by multiplex ligation-dependent probe amplification

et al. 2012

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IntroductionEpigenetic events are, along with genetic alteration, important in the development and progression of cancer. Promoter hypermethylation causes gene silencing and is thought to be an early event in carcinogenesis. The role of promoter hypermethylation in male breast cancer has not yet been studied.MethodsIn a group of 108 male breast cancers, the methylation status of 25 genes was studied using methylation-specific multiplex ligation-dependent probe amplification. Methylation of more than 15% was regarded indicative for promoter hypermethylation. Methylation status was correlated with clinicopathological features, with patients' outcome and with 28 female breast cancer cases.ResultsPromoter hypermethylation of the genes MSH6, WT1, PAX5, CDH13, GATA5 and PAX6 was seen in more than 50% of the cases, but was uncommon or absent in normal male breast tissue. High overall methylation status was correlated with high grade (P = 0.003) and was an independent predictor of poor survival (P = 0.048; hazard ratio 2.5). ESR1 and GSTP1 hypermethylation were associated with high mitotic count (P = 0.037 and P = 0.002, respectively) and high grade (both P = 0.001). No correlation with survival was seen for individual genes. Compared with female breast cancers (logistic regression), promoter hypermethylation was less common in a variety of genes, particularly ESR1 (P = 0.005), BRCA1 (P = 0.010) and BRCA2 (P < 0.001). The most frequently hypermethylated genes (MSH6, CDH13, PAX5, PAX6 and WT1) were similar for male and female breast cancer.ConclusionPromoter hypermethylation is common in male breast cancer and high methylation status correlates with aggressive phenotype and poor survival. ESR1 and GSTP1 promoter hypermethylation seem to be involved in development and/or progression of high-grade male breast cancer. Although female and male breast cancer share a set of commonly methylated genes, many of the studied genes are less frequently methylated in male breast cancer, pointing towards possible differences between male and female breast carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Promoter hypermethylation in male breast cancer: analysis by multiplex ligation-dependent probe amplification

et al. 2012

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“…The seven classes of GSTs (a, m, p, s, q, k, z) have considerable substrate promiscuity, with different catalytic efficiencies (24,25). Most studies have focused on the various polymorphisms of the GSTs in breast cancer and drug resistance, although the resistance to various anticancer agents has also been linked to the overexpression of GSTs in tumor cells (26)(27)(28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

Redox Protein Expression Predicts Radiotherapeutic Response in Early-Stage Invasive Breast Cancer Patients

Al‐Attar

Storr

Ellis

et al. 2011

International Journal of Radiation Oncology*Biology*Physics

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“…In addition, integrated analysis showed GSTP1 and PALLD genes having low level gene expression as well as significantly higher methylation level of these gene promoters in luminal phenotype compared to the other two subtypes. Hypermethylation of the GSTP1 promoter has also been previously reported as having association with prognostic values [52], and repression of PALLD gene has been shown to contribute to invasive motility [53] and cancer cell migration [54]. Including these genes, a large number of detected genes from our analysis have overlapping of promoter regions with DHS region as well as polycom-associated H3K27me3 marked region, suggesting a potential interplay with gene transcription and that differential methylation may play important roles across the subtypes.…”

Section: Discussionmentioning

confidence: 99%

Subtype-specific CpG island shore methylation and mutation patterns in 30 breast cancer cell lines

et al. 2016

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BackgroundAberrant epigenetic modifications, including DNA methylation, are key regulators of gene activity in tumorigenesis. Breast cancer is a heterogeneous disease, and large-scale analyses indicate that tumor from normal and benign tissues, as well as molecular subtypes of breast cancer, can be distinguished based on their distinct genomic, transcriptomic, and epigenomic profiles. In this study, we used affinity-based methylation sequencing data in 30 breast cancer cell lines representing functionally distinct cancer subtypes to investigate methylation and mutation patterns at the whole genome level.ResultsOur analysis revealed significant differences in CpG island (CpGI) shore methylation and mutation patterns among breast cancer subtypes. In particular, the basal-like B type, a highly aggressive form of the disease, displayed distinct CpGI shore hypomethylation patterns that were significantly associated with downstream gene regulation. We determined that mutation rates at CpG sites were highly correlated with DNA methylation status and observed distinct mutation rates among the breast cancer subtypes. These findings were validated by using targeted bisulfite sequencing of differentially expressed genes (n=85) among the cell lines.ConclusionsOur results suggest that alterations in DNA methylation play critical roles in gene regulatory process as well as cytosine substitution rates at CpG sites in molecular subtypes of breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12918-016-0356-2) contains supplementary material, which is available to authorized users.

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Hypermethylation of the GSTP1 promoter region in breast cancer is associated with prognostic clinicopathological parameters

Abstract: breast cancer, prognostic factors, hypermethylation, GSTP1, methylation-specific PCR.

Cited by 22 publications

References 30 publications

Promoter hypermethylation in male breast cancer: analysis by multiplex ligation-dependent probe amplification

Promoter hypermethylation in male breast cancer: analysis by multiplex ligation-dependent probe amplification

Redox Protein Expression Predicts Radiotherapeutic Response in Early-Stage Invasive Breast Cancer Patients

Subtype-specific CpG island shore methylation and mutation patterns in 30 breast cancer cell lines

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